Clinical depression is a medical condition that goes beyond everyday sadness. Depression may cause serious, long-lasting symptoms and often disrupts a person’s ability to perform routine tasks. The disorder is the most common psychiatric disorder worldwide. In the United States, about one in six people experiences a bout of clinical depression in their lifetime.

The treatment of depression is important because people with untreated depression have a lower quality of life, a higher risk of suicide, and worse physical outcomes if they have any medical conditions besides depression. In fact, people with depression are almost twice as likely to die as people without the condition. What’s more, depression affects not only the people with the disorder but also those around them.

Briefly, to be diagnosed with unipolar major depression, a person must have five or more of the following symptoms present most of the day nearly every day for at least two consecutive weeks. For the diagnosis, at least one symptom must be either depressed mood or loss of interest or pleasure.

●Depressed mood

●Loss of interest or pleasure in most or all activities

●Change in appetite or weight

●Insomnia or hypersomnia (sleeping too little or too much)

●Psychomotor agitation or retardation (restlessness or sluggishness)

●Fatigue or loss of energy

●Feelings of worthlessness or excessive guilt

●Poor concentration

●Recurrent thoughts of death or suicide

For the purposes of this discussion, we will use depression to mean unipolar major depression. There are other subtypes of depression, as well, but those are beyond the scope of this article.

TREATMENT DEPENDENT ON DEPRESSION SEVERITY

Healthcare providers approach the treatment of depression differently depending on its severity. The following descriptions explain how the different severity levels are defined.

Mild to moderate depression — People with mild to moderate depression have the following characteristics:

●They do NOT have thoughts of or plans for suicide or homicide.

●They do NOT have psychotic symptoms, such as delusions or hallucinations.

●They have little to no aggressiveness.

●Their judgement is intact.

People with mild to moderate depression can generally be treated during routine visits with a healthcare provider; they do not typically need to be hospitalized.

Severe depression — People with severe major depression have one or more of the following characteristics:

●They DO have thoughts of and plans for suicide or homicide.

●They DO have psychotic symptoms, such as delusions or hallucinations.

●They have a condition called catatonia, which involves being unable to move or talk normally.

●Their judgement is impaired such that people (including themselves) may be at risk for harm.

●Their normal functioning is impaired. For example, they may refuse to eat or drink which may lead to malnourishment or dehydration.

People with severe major depression usually need to be seen by a psychiatrist and sometimes need to be hospitalized.

TREATMENT FOR MILD TO MODERATE DEPRESSION

For the initial treatment of mild to moderate depression, we suggest a combination of antidepressant medication and psychotherapy. Well-designed studies have shown that combination treatment is more effective than either treatment on its own. Nevertheless, either treatment can also be given alone, as studies have also shown that each is effective and comparable to the other.

Despite being comparably effective, one advantage of psychotherapy is that some of its benefits often persist even after active treatment ends. Psychotherapy may help people develop new coping skills as well as more adaptive ways of thinking about life problems. The same is not necessarily true of antidepressants; many who take antidepressants alone relapse after stopping them.

ANTIDEPRESSANTS

Individual medications are grouped into what healthcare providers call classes. All the medications within a particular class are chemically related and function in a similar way. Medications are also grouped into generations based on when they were developed and how much their chemistry has been fine-tuned. In the case of antidepressants, there are many different classes and a couple of generations. The more commonly used medications are from the following classes, all of which are second-generation:

●Selective serotonin reuptake inhibitors (SSRIs)

●Serotonin-norepinephrine reuptake inhibitors (SNRIs)

●Atypical antidepressants

●Serotonin modulators

Older, less commonly used, first-generation antidepressants tend to have a less targeted effect on the brain and can cause more side effects. Examples of these include:

●Tricyclic antidepressants

●Monoamine oxidase inhibitors (MAOIs)

Selecting an antidepressant — For people with mild to moderate depression who start treatment with an antidepressant, we suggest SSRIs. Among the different antidepressants choices, SSRIs offer the most benefit with the least amount of risk or side effects. They are the most widely prescribed class of antidepressants.

●The other medications the person is taking and whether they could interact with the antidepressant choice

●The response the person’s close family members have had to antidepressants

●Each medication’s ease of use (for example based on the number of pills the person must take each day)

●What the person prefers

●The cost of a medication and whether it is covered by insurance

For example, for people who have trouble sleeping, healthcare providers often favor antidepressants known to promote sleep, such as mirtazapine. Similarly, for people who want to avoid the sexual side effects caused by many antidepressants, healthcare providers might favor bupropion, which is less likely to cause these side effects.

Side effects — The table lists the most common side effects for the main available antidepressants and how likely each set of side effects is to occur (table 2A-B). Some side effects (such as nausea) are common to many of the antidepressants, while others are more medication-specific. However, some side effects, including nausea, are often temporary and go away after a few days or weeks of use.

Dose — In general, healthcare providers tend to start their patients on low doses and slowly increase them as necessary. This helps minimize the likelihood of side effects.

How long before antidepressants take effect? — Antidepressants often take time to work, but many people start to feel better within one to two weeks. In fact, the people who see some benefit early on after starting an antidepressant appear to be the ones most likely to completely recover. That being said, it can take 6 to 12 weeks to see the full effect of an antidepressant, so healthcare providers generally wait that long to determine whether a particular medication or dose is effective. Still, if a person is not getting much or any relief from his or her symptoms after 4 to 6 weeks, it may make sense to increase a dose, add an additional medication, or take some other next step.

The important thing to keep in mind when starting an antidepressant is that each person’s individual response is different, and the medications take some time to take effect. If you are put on an antidepressant, give it a few weeks to start working. But if you don’t see a benefit within 4 to 6 weeks, tell your healthcare provider. It’s possible that you need to try higher dose, a different medication, or an additional medication. Likewise, if you are having uncomfortable side effects, tell your healthcare provider about those, too. Some side effects go away over time, but others do not, and it might be possible to find a dose or alternate medication that causes fewer side effects.

The point is, finding the right medication or combination of medications and the right doses sometimes takes a bit of trial and error. But it’s important not to get discouraged. Effective medications are out there, if you are willing to work with your provider to find the one that’s best for you.

PSYCHOTHERAPY

There are many different types of psychotherapy, called modalities, which are used to treat depression. Each of these modalities works in a slightly different way, but all have been proven to help improve the symptoms of depression. What’s more, many psychotherapists use a combination of techniques when working with clients. The modality options include the following:

●Cognitive-behavioral therapy (CBT) – In CBT you work with a therapist to identify and reshape the thought and behavior patterns that contribute to your depression.

●Interpersonal psychotherapy – In interpersonal psychotherapy, you focus on your relationships, the way that you interact with other people in your life, and the different roles you play. Often you learn new ways to interact that can help improve those relationships

●Family and couples therapy – In family and couples therapy, you attend therapy sessions along with your partner or family members so that you can work together on the issues that are contributing to your depression.

●Problem solving therapy – In problem-solving therapy you take a very pragmatic and systematic approach to the problems in your life. If you are unemployed, for example, you work with your therapist to explore what might be holding you back from finding a job. Then you explore ways to overcome those obstacles.

Selecting a psychotherapy — If there’s a particular form of psychotherapy that appeals to you more than another, ask the therapist you are thinking of working with whether he or she uses that form of therapy. Keep in mind, though, that the most important aspect of psychotherapy is the relationship and rapport you have with therapist you choose.

Clinician guided self-help — Instead of attending formal therapy sessions, some people opt to work on their own with a little guidance from a healthcare provider. This approach is called clinician guided self-help and involves the use of workbooks (hardcopy, compact disc, or internet-based), audiotapes, or videotapes. People who choose this approach check in periodically with their healthcare provider but the interactions are much more brief and infrequent compared with formal therapy.

Guided self-help can be a good choice for people who have mild depression and have no thoughts of death or suicide. People who fall into this category can even try self-help approaches on their own, without checking in with a healthcare provider, unless their symptoms start to get worse.

Psychotherapy compared with antidepressants — Research shows that psychotherapy is about as effective as antidepressants in treating people with mild to moderate depression. One advantage of psychotherapy is that its benefits often last even after treatment stops, whereas those of antidepressants wear off fairly quickly, once the antidepressant is stopped or tapered. For that reason, people who stop taking antidepressants may be more likely to relapse than those who stop psychotherapy. This is another reason why combining psychotherapy and antidepressants may be the best approach.

Relaxation, exercise, and positive activities — We suggest combining formal treatment with some add-on activities that seem to help alleviate depression. Among these are relaxation techniques (such as progressive muscle relaxation) and exercise. We also suggest that people resume the activities they stopped doing because of their depression. People sometimes think that once their depression lifts, they’ll go back to doing those activities, but it turns out that doing those activities—even while still depressed—can help turn the depression around.

Exercise in particular may have an especially positive effect on depression. Several studies suggest that exercise can ease depression. We suggest three to five exercise sessions per week, that last 45 to 60 minutes per session, for at least 10 weeks, and involve aerobic exercise (such as walking, running, or cycling) or resistance training (upper and lower body weight lifting).

Anxiety and insomnia — Many people with depression also have problems with anxiety and sleeplessness. Antidepressants can help with both of those symptoms but sometimes take a while to start working. If you are very anxious or having a very hard time sleeping, your healthcare provider can prescribe medications to deal with both while you wait for your antidepressants start working.

TREATMENT FOR SEVERE MAJOR DEPRESSION

For people with severe depression, we suggest a combination of antidepressant medication and psychotherapy. It’s also reasonable to try antidepressants alone. (Psychotherapy is generally not used alone for patients with severe depression.) Another reasonable treatment for severe depression is electroconvulsive therapy (ECT), particularly in people who are actively thinking about suicide and who may be in danger of following through on their plans. ECT is discussed at elsewhere (See "Patient information: Electroconvulsive therapy (ECT) (Beyond the Basics)".)

Choosing an antidepressant — For the initial treatment of severe depression, we use serotonin-norepinephrine reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs). In people who have symptoms besides those of depression, additional medications such as atypical antipsychotics may be appropriate.

Some healthcare providers start with SNRIs because studies suggest that these medications are more likely than SSRIs to alleviate severe depression. A reasonable alternative to SNRIs or SSRIs is a medication called mirtazapine (brand name: Remeron). It, too, has been shown to be effective in treating severe depression.

Tricyclic antidepressants are another reasonable alternative for severe depression. However, tricyclics can be dangerous and cause serious side effects, so some healthcare providers prefer to avoid prescribing them until safer alternatives have been tried.

DEPRESSION AND PREGNANCY

Women who have depression and want to become pregnant or who develop depression while pregnant sometimes have a tough decision to make regarding the use of antidepressants. Taking antidepressants during pregnancy may increase the risk of miscarriage, premature delivery, and low birth weight. Studies examining whether there has been an increased rate of birth defects associated with taking antidepressants in pregnancy have been inconsistent with some showing higher risk and others showing no increased risk. On the other hand, leaving depression untreated during pregnancy increases the risk of premature delivery, low birth weight, missed obstetrical appointments, anorexia, suicidality and other depressive symptoms, and substance (drug and alcohol) use disorders. Given these risks, women must work with their healthcare providers to weigh the pros and cons of using antidepressants to treat depression during pregnancy.

The risks of antidepressants, generally speaking, are small, and they vary based on which specific medication is used, the dose, the duration of use, and when during the course of the pregnancy the medication is used. Still, because risks do exist, experts recommend avoiding antidepressants or minimizing their use during pregnancy whenever possible. Among the different choices, the SSRIs sertraline (brand name: Zoloft) and citalopram (brand name: Celexa) appear to confer the lowest risks to the fetus.

Planning to become pregnant — Women who would like to become pregnant and are on antidepressants should discuss their plans with a healthcare provider. Women who are no longer depressed but are still taking antidepressants may want to consider going off them for their pregnancy. Studies show that women who stop antidepressants during pregnancy are more likely to relapse than women who continue medication. On the other hand, stopping the medications may lower risks to the baby.

Women who are still depressed and on antidepressants should wait until their depression lifts and they have been stable for six months or longer before they consider getting pregnant. At that point they can reevaluate whether to stay on the medications or try to go off them.

Women who prefer to stay on antidepressants during pregnancy and are taking medications other than sertraline (brand name: Zoloft) or citalopram (brand name: Celexa) may want to switch to one of these medications before they attempt to get pregnant. Sertraline and citalopram seem to be the safest among the antidepressants for developing fetus. However, switching antidepressants may increase the risk of relapse.

Already pregnant — Here are the main recommendations regarding the treatment of depression in women who are already pregnant:

●Women who get pregnant while on antidepressants and want to go off them should do so slowly, not all at once, with guidance and input from a healthcare provider.

●For pregnant women with mild to moderate depression, experts suggest psychotherapy as initial treatment, rather than antidepressants. Antidepressants are a reasonable choice if psychotherapy is unsuccessful or not an option. Antidepressants are also a reasonable option for women who responded well to medications for past episodes of depression and for women with a history of severe depression.

●For pregnant women with severe depression, experts suggest selective serotonin reuptake inhibitors (SSRIs) as initial treatment, rather than other antidepressants. Among the SSRIs, favored options include sertraline or citalopram. Paroxetine is generally not recommended due to concerns about possible birth defects. Psychotherapy, in addition to antidepressants, may also be helpful.

●For pregnant women who are no longer depressed but who are taking antidepressants to prevent relapse, it is worth considering discontinuing medications for the first trimester—during which the baby’s organs are formed. These women can then restart treatment during the second trimester. Of course, any time antidepressants are stopped, there is a chance of relapse and such a decision should be discussed with a healthcare provider.

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.